Helical-Peptide-Catalyzed Enantioselective Michael Addition Reactions and Their Mechanistic Insights

Helical peptide foldamer catalyzed
Michael addition reactions of
nitroalkane or dialkyl malonate to α,β-unsaturated ketones
are reported along with the mechanistic considerations of the enantio-induction.
A wide variety of α,β-unsaturated ketones, including β-aryl,
β-alkyl enones, and cyclic enones, were found to be catalyzed
by the helical peptide to give Michael adducts with high enantioselectivities
(up to 99%). On the basis of X-ray crystallographic analysis and depsipeptide
study, the amide protons, N(2)–H and N(3)–H, at the
N terminus in the α-helical peptide catalyst were crucial for
activating Michael donors, while the N-terminal primary amine activated
Michael acceptors through the formation of iminium ion intermediates.